Devereux T R, Risinger J I, Barrett J C
Environmental Carcinogenesis Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.
IARC Sci Publ. 1999(146):19-42.
To understand the causes of cancer, it is necessary to elucidate the molecular basis and environmental factors that influence the carcinogenesis process. Cancers are progressive diseases characterized by the accumulation of defects in many different genes. The patterns of mutation of some genes identified in tumours suggest a direct action of chemicals binding to and altering DNA. Other cancer-associated genes may be altered as a consequence of endogenous mutagens, germ-line mutations, spontaneous mutations that occur during cell replication or increased genetic instability in precancerous cells. Recent advances in molecular biology and genetics have provided new tools and concepts for studying the causes of cancer. We know that cancers are caused by a combination of environmental and genetic factors, and the discovery of the molecular alterations that occur at various stages in different tumours is increasing our understanding of these causes. Thus, we are now beginning to discover which genes are involved, how they function normally and in tumour tissues and why cancers develop after a series of genetic and epigenetic changes in certain cells. As data from studies on cancer-associated genes have accrued, the categories of genes and molecular pathways that have been found to play a role in carcinogenesis have also increased. Genes involved in development and other normal cellular processes have been implicated in cancer. These include genes involved in signal transduction, cell cycle control, DNA repair, cell growth and differentiation (growth factors and growth factor receptors), transcriptional regulation, senescence and apoptosis. Genes involved in angiogenesis, immune regulation, cellular responses to stress, motility, adhesion and invasion are also involved, but less is known about their relationship to carcinogenesis, and these processes are not discussed in this review. The diverse nature of these categories of cancer-related genes indicates the variety of processes that must be disrupted in order for tumours to develop. Many of the genes have several functional domains, and the functions of some have only recently been proposed. In this review, we describe some of the major classes of genes implicated in human cancers and some of the major findings on genetic alterations and dysfunction in human tumours. Comparisons are made with certain rodent models.
为了了解癌症的病因，有必要阐明影响致癌过程的分子基础和环境因素。癌症是一种进展性疾病，其特征是许多不同基因中缺陷的积累。在肿瘤中鉴定出的一些基因的突变模式表明化学物质与DNA结合并改变DNA的直接作用。其他与癌症相关的基因可能由于内源性诱变剂、种系突变、细胞复制过程中发生的自发突变或癌前细胞中遗传不稳定性增加而发生改变。分子生物学和遗传学的最新进展为研究癌症病因提供了新的工具和概念。我们知道癌症是由环境和遗传因素共同引起的，不同肿瘤在各个阶段发生的分子改变的发现正在加深我们对这些病因的理解。因此，我们现在开始发现哪些基因参与其中，它们在正常组织和肿瘤组织中如何发挥作用，以及为什么癌症会在某些细胞发生一系列遗传和表观遗传变化后发展。随着与癌症相关基因研究数据的积累，已发现参与致癌作用的基因类别和分子途径也有所增加。参与发育和其他正常细胞过程的基因与癌症有关。这些基因包括参与信号转导、细胞周期控制、DNA修复、细胞生长和分化（生长因子和生长因子受体）、转录调控、衰老和凋亡的基因。参与血管生成、免疫调节、细胞对应激的反应、运动、黏附和侵袭的基因也与癌症有关，但对它们与致癌作用的关系了解较少，本综述不讨论这些过程。这些与癌症相关的基因类别的多样性表明，为了使肿瘤发展，必须破坏多种过程。许多基因有几个功能域，其中一些基因的功能直到最近才被提出。在本综述中，我们描述了一些与人类癌症相关的主要基因类别，以及关于人类肿瘤中遗传改变和功能障碍的一些主要发现。并与某些啮齿动物模型进行了比较。
